title: Macromolecular prodrugs for controlled delivery of ribavirin.
abstract: Ribavirin (RBV)-containing polymers are synthesized based on poly(N-vinylpyrrolidone) and poly(acrylic acid), two polymers with extensive characterization in biomedicine. The copolymers are shown to exhibit a minor to negligible degree of association with erythrocytes, thus effectively eliminating the origin of the main side effects of RBV. The therapeutic benefit of macromolecular RBV prodrugs is illustrated by matched efficacy in suppressing production of nitric oxide by stimulated cultured macrophages as compared to pristine RBV with no associated cytotoxicity, which is in stark contrast to an RBV-based treatment which results in a significant decrease in cell viability. These results contribute to the development of antiviral polymer therapeutics and delivery of RBV in particular.
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO), Gustav WiedsVej 14, DK-8000, Aarhus C, Denmark.
authors.forename: Mille B L
authors.initials: MB
authors.lastname: Kryger
authors.forename: Anton A A
authors.initials: AA
authors.lastname: Smith
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Wohl
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Zelikin
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000998:Antiviral Agents / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry; D012254:Ribavirin / Q000008:administration & dosage*
chemical_list: D000180:Acrylic Resins; D000998:Antiviral Agents; D011145:Polyvinyls; D011355:Prodrugs; D011760:Pyrrolidinones; C099680:poly(1-vinyl-2-pyrrolidinone); D009569:Nitric Oxide; D012254:Ribavirin; C006903:carbopol 940
keywords: antiviral therapy; hepatitis; inflammation; polymer therapeutics; ribavirin